Support is requested for a Keystone Symposia meeting entitled Gram-Negative Resistance, organized by Robert E.W. Hancock and Eric D. Brown. The meeting will be held in Tahoe City, California from March 29 - April 2, 2015. The antibiotic era, stemming from the deployment of penicillin, introduced arguably the most successful medicines of all time, impacting dramatically on life expectancy by decreasing childhood and adult deaths from infections, and enabling complex surgeries, transplantations and cancer chemotherapy. However the therapy of infectious diseases is now under severe threat. There has been an explosion of resistance to antibiotics, whereby our entire arsenal of antibiotics is gradually losing effectiveness. This is particularly acute for gram-negative bacteri since there are few new antibiotics or strategies in the development pipeline. This Keystone Symposia meeting will address the major issues and potential solutions to this crisis. The issues associated with gram-negative resistance, and the design of effective therapeutics, are different and more complicated than those associated with the other major division of bacteria (gram-positives). Consistent with the most recent antibiotics are active against the latter class leaving academic and company researchers and physicians to wonder where the next generation of treatments will come from. For this reason, it is essential that these issues are discussed as a distinct problem that has the potential to unravel human medical successes. This meeting will bring together diverse researchers from disciplines ranging from discovery research to drug development and clinical treatment to discuss strategies for addressing this critical issue and proposing routes for innovative solutions. Support of this conference is consistent with the statement that Discoveries made by NIAID researchers help inform the development of new vaccines, therapeutics, and diagnostics that improve human health.